共查询到20条相似文献,搜索用时 31 毫秒
1.
Kambouris M Banjar H Moggari I Nazer H Al-Hamed M Meyer BF 《European journal of pediatrics》2000,159(5):303-309
The cystic fibrosis transmembrane regulator (CFTR) gene in Arab patients with cystic fibrosis (CF) (sweat chloride >60 mmol/l)
from 61 unrelated families was screened for mutations in exons 3, 4, 5, 7, 10, 11, 16 and 19 and for mutations W1282X, N1303K
and 3849 + 10kbC → T. Eight novel mutations were identified. These are: in exon 4: a) 425del42 (an in-frame 42 bp deletion
that removes 14 amino acids and causes Gln98 → His at the point of deletion), b) 475G → T (Glu115 → Stop) and c) 548A → T (His139 → Leu); in intron 5, 711 + 1G → A (splice site mutation); in exon 10, 1548delG (deletion of a “G” nucleotide causing a frameshift
mutation that alters the amino acid sequence at residue 473 and results in translation termination at residue 526); in exon
11, a) 1729T → C (Ph533E → Leu) and b) 1811 + 2 (splice site mutation) and finally in exon 19, 3361A → T (Lys1177 → Stop). All mutations were detected by heteroduplex analysis and identified by sequencing. Of more than 850 known CFTR mutations,
only 9 were encountered. The comparative frequencies of the most common mutations are: 1548delG> I123V=ΔF508=3120 + 1G → A > H139L.
Screening for these five mutations identifies 60% of the CF alleles in Arab populations. The novel mutation 1548delG is the
most frequent (17%) among Arabs.
Conclusion Novel Arab-specific mutations were identified in the CFTR gene underlying cystic fibrosis. As a result of this study, the CFTR mutation detection rate among Arabs with cystic fibrosis is now comparable to that of other populations.
Received: 18 December 1998 / Accepted: 14 May 1999 相似文献
2.
Y. Maruo S. Wada K. Yamamoto H. Sato T. Yamano M. Shimada 《European journal of pediatrics》1999,158(7):547-549
Gilbert syndrome was diagnosed in a girl with anorexia nervosa and unconjugated hyperbilirubinaemia. Since the patient was
starved and hyperbilirubinaemic, the loading test was not used for the diagnosis but analysis of the bilirubin UDP-glucuronosyltransferase
gene (UGT1A1) instead. The patient was homozygous for a missense mutation that replaced guanine with adenine at nucleotide number 211
(211G→A: G71R). The unconjugated hyperbilirubinaemia was apparently induced by the fasting state. Homozygous missense mutations
of the gene have been generally recognized as responsible for Crigler-Najjar syndrome type II; the results obtained here,
however, confirm that Gilbert syndrome may also be caused by a homozygous missense mutation of UGT1A1.
Conclusion Since anorexia nervosa patients are in a fasting state, they may show moderate unconjugated hyperbilirubinaemia if they have
Gilbert syndrome. Gene analysis of such cases will rule out hepatic damage. Homozygous missense mutations of the bilirubin-UDP-glucuronosyltransferase
gene cause not only Crigler-Najjar syndrome type II but also Gilbert syndrome.
Received: 18 August 1998 / Accepted: 3 December 1998 相似文献
3.
G. M. C. Kuijpers M. De Vroede H. E. Knol M. Jansen 《European journal of pediatrics》1999,158(6):451-454
Growth retardation is a consistent finding in Williams-Beuren syndrome. The cause of short stature in this syndrome is unknown.
Endocrine studies have failed to reveal abnormalities in the growth hormone – insulin-like growth factor I axis. We report
a boy with confirmed Williams-Beuren syndrome, who was found to have classical growth hormone deficiency and responded well
to growth hormone therapy.
Conclusion Although growth hormone deficiency is not likely to be a common cause of short stature in Williams-Beuren syndrome, we nevertheless
recommend evaluation of the growth hormone – insulin-like growth factor I axis in all cases.
Received: 14 February 1998 / Accepted in revised form: 4 April 1998 相似文献
4.
Sakamoto O Suzuki Y Li X Aoki Y Hiratsuka M Holme E Kudoh J Shimizu N Narisawa K 《European journal of pediatrics》2000,159(1-2):18-22
Holocarboxylase synthetase (HCS) deficiency is a disorder of biotin metabolism characterised by metabolic ketoacidosis and
skin lesions due to reduced activities of multiple biotin-dependent carboxylases. The onset of this disease is usually between
the neonatal and infantile period. Here we report the molecular analysis of an atypical case of HCS deficiency, where the
patient developed his first episode of acidosis at age 8 years and had an exceptionally slow response to biotin therapy. A
homozygous mutation was identified at the +5 position of the splice donor site in intron 10 of the HCS gene (IVs10 + 5(g → a)),
resulting in abnormal splicing of HCS mRNA. A moderate decrease in the amount of normal HCS mRNA may account for the atypical,
late-onset phenotype of this patient.
Conclusion Molecular analysis is a useful tool for understanding the phenotypic variations in holocarboxylase synthetase deficiency.
Received: 8 October 1998 and in revised forms: 1 February 1999 and 4 April 1999 / Accepted: 10 April 1999 相似文献
5.
P. Huppke D. Wünsch A. Pekrun R. Kind H. Winkler W. Schröter M. Lakomek 《European journal of pediatrics》1997,156(8):605-609
Biochemical and molecular genetic studies were performed on the enzyme variants of two patients compound heterozygous for
glucose phosphate isomerase (GPI) deficiency, both suffering from severe haemolytic anaemia. The enzymes of case 1 (GPI `Zwickau')
and case 2 (GPI `Nordhorn' [25]), revealed reduced GPI activity and remarkable thermolability. Glucose-6-phosphate (Gluc-6-P)
concentration was elevated 2.3 times in case 1 and 3.8 times in case 2. Sequencing the patients' GPI genes showed four different
point mutations, two of them involving highly conserved amino acids. The c1039 C→T substitution, found in the gene of GPI
`Zwickau', has been described recently [30] and causes an Arg 347→Cys substitution close to the putative catalytic site. The
second mutation in this case is a novel c1538 G→A substitution causing a Trp→stop mutation at position 513 apparently resulting
in premature RNA degradation thus resulting either in a complete lack of protein or a protein which does not show GPI activity.
In the gene of GPI `Nordhorn' a c1028 A→G mutation was discovered, also previously described [1, 9] causing a Gln 343→Trp
substitution. The second mutation was a novel splice site mutation at the border of intron 15 to exon 16: IVS15-(-2) A→C which
leads to an aberrant splicing of exon 16, thus resulting either in a truncated and most likely inactive enzyme or in no protein
at all.
Conclusion Biochemical and molecular genetic studies performed with the enzyme variants GPI `Zwickau' and GPI `Nordhorn' showed that
in both cases the simultaneous occurrence of a single amino acid sub‐stitution affecting the active site, together with a
nonsense mutation leading to the loss of major parts of the enzyme probably explains the severe clinical course of the disease.
Received: 16 August 1996 / Accepted: 17 January 1997 相似文献
6.
D. Fabri V. M. S. Belangero J. M. Annichino-Bizzacchi V. R. Arruda 《European journal of pediatrics》1998,157(11):939-942
A hereditary tendency to venous thrombosis rarely results in a spontaneous thrombotic episode before puberty. The acquired
hypercoagulability associated with nephrotic syndrome (NS) could, however, coincide with underlying inherited thrombophilia,
thereby resulting in a thrombotic event. In order to determine the contribution of inherited prothrombotic conditions to thrombosis
in children with NS, we analysed DNA from a cohort of patients with NS for the common genetic risk factors of vascular disease.
We evaluated 53 children with NS and 41 paediatric controls for prevalence of the factor V mutation Arg506→Gln (factor V Leiden),
the prothrombin variant (20210G→A), and homozigosity for Ala677→Val in the methylenetetrahydrofolate reductase gene (MTHFR).
Eight thrombo-embolic events were identified in 6 out of 53 (11%) children. Three thrombotic events occurred during NS activity
and were associated with systemic infections in two and an arterial puncture in one. An inherited risk factor was identified
in seven children, all without thrombosis (two heterozygous for the prothrombin variant and five homozygous for the MTHFR-T).
None of the studied inherited risk factors were identified among those with thrombosis.
Conclusions These data suggest that inherited thrombophilia is not a strong risk factor for the development of non recurrent thrombosis
in children with NS.
Received: 21 October 1997 / Accepted in revised form: 12 April 1998 相似文献
7.
Short stature is a common problem in patients with myelomeningocele (MMC) and hydrocephalus. We evaluated auxological and
laboratory parameters to differentiate short stature due to neurological defect from short stature additionally caused by
growth hormone deficiency (GHD). In a group of 38 prepubertal patients with MMC and hydrocephalus aged 3.8–11.0 years, auxological
parameters, including arm span and bone age, and serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor
binding protein-3 (IGFBP-3) levels were measured. Patients with normal supine length (n = 15) had normal arm span. Serum IGF-1 and IGFBP-3 levels were normal (≥ 10th percentile) in 14/15 patients. Twenty-three
MMC patients had short stature (height SDS < −2), 11/23 patients had reduced arm span (SDS < −2), and 12/23 had normal arm
span. Serum IGF-1 and IGFBP-3 levels were normal in 10/12 of short statured patients with normal arm span, but low (<10th
percentile) in those patients with reduced arm span (IGF-1: 8/11 patients, P<0.05; IGFBP-3: 9/11 patients, P<0.005). In 7/11 short statured MMC patients with reduced arm span and low serum IGF-1 and IGFBP-3 levels, growth hormone
secretion was investigated. All had a disturbed growth hormone secretion (GHD: n = 4; neurosecretory dysfunction: n = 3).
Conclusion Arm span, serum IGF-1 and IGFBP-3 levels are estimated to be appropriate screening parameters for GHD in patients with MMC.
Initiating growth hormone therapy should be considered not only according to endocrine findings but also with respect to neurological
and orthopaedic anomalies.
Received: 27 March 1997 / Accepted: revised form 18 September 1997 相似文献
8.
B. H. P. Nagel M. Palmbach D. Petersen M. B. Ranke 《European journal of pediatrics》1997,156(10):758-763
In order to validate an association between pituitary size and severity of growth hormone deficiency (GHD) we evaluated the
magnetic resonance images (MRI) of 107 children with different causes of short stature. Ninety-one MRIs were evaluable (64
male, 27 female; age: 9.1 ± 3.9 years). The levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor
binding protein-3 (IGFBP-3), and tests of GH stimulation and spontaneous secretion, led to the following sub-groups: severe
isolated GHD (SIGHD) (GH < 7 ng/ml) (n = 21); partial, isolated GHD (GH 7–10 ng/ml) (n = 22); multiple pituitary hormone deficiency (MPHD) (n = 13); neurosecretory dysfunction (n = 10); non-classifiable diagnosis (NC) (n = 13); idiopathic short stature (n = 9); and intra-uterine growth retardation (n = 3). Pituitary height (PHT) was measured and hypoplasia was assumed when PHT was <−2 SDS. An ectopic posterior pituitary
with missing stalk and a hypoplastic anterior pituitary was present in 12 (57%) SIGHD cases, 12 (92%) MPHD cases and 1 patient
from the NC group. An isolated hypoplastic anterior pituitary was observed in 15%−33% of the other groups. PHT (mm; mean,
SD) in MPHD (1.7 ± 0.5) was lower than in SIGHD (2.7 ± 1.0, P < 0.05), with PHT of both groups being lower than in all the other groups (3.8 ± 0.9, P < 0.0001). PHT SDS correlates with IGF-I SDS (r = 0.48, P < 0.0001), IGFBP-3 SDS (r = 0.46, P < 0.0001) and the highest peaks in tests of GH stimulation and GH spontaneous secretion (r = 0.36, P < 0.0001). In contrast to all the other groups, no correlation with age was observed in MPHD and SIGHD. Breech delivery was
recorded in up to 26% of patients in all seven groups. Surprisingly, only 1 out of 23 patients with an ectopic posterior pituitary
was born by breech delivery, suggesting that ectopia of the posterior lobe is not necessarily related to breech delivery.
Conclusion PHT is significantly correlated with GH secretion in several types of short stature. Patients with␣ectopic posterior pituitary,
missing stalk and hypoplastic␣anterior pituitary either suffer from SIGHD or MPHD, and this anatomical defect is not necessarily
related to breech delivery.
Received: 1 December 1996 and in revised form: 8 February 1997 / Accepted: 18 February 1997 相似文献
9.
H. Bucher S. Rampini R. W. James D. Pometta H. Funke H. Wiebusch G. Assmann 《European journal of pediatrics》1997,156(2):121-125
Clinical and biochemical characteristics of a female patient with familial lipoprotein lipase deficiency have been followed
in short intervals before and during puberty. The proband is compound heterozygote for two missense mutations in the lipoprotein
lipase gene. One mutation occurs in codon 250 (Asp250→Asn), the other is in codon 410 (Glu410→Lys). The residual lipoprotein lipase activity in the proband is less than 10% of controls. Before puberty the proband usually
presented with moderate isolated hypertriglyceridaemia. During the initial phase of puberty a dramatic increase in the plasma
concentration of both cholesterol and triglycerides was observed. During the second half of puberty a reduction of cholesterol
but not of triglycerides was noticed.
Conclusion These findings show that the phenotypic expression of familial chylomicronaemia can be modified to a large extent by hormones.
Furthermore they demonstrate the need for a closer clinical observation of type Ι patients during puberty.
Received: 29 March 1996 / Accepted: 1 August 1996 相似文献
10.
A. E. Melin L. Adan G. Leverger J. C. Souberbielle G. Schaison R. Brauner 《European journal of pediatrics》1998,157(9):703-707
The dose of prophylactic cranial irradiation given to patients for acute lymphoblastic leukaemia has been decreased from
24 to 18 Gy, but the beneficial effect of this decrease on growth is controversial.
This study compares the growth hormone (GH) secretion and growth of 35 patients (20 boys) given 18 Gy at 3.7 ± 0.3 (SE) years,
and routinely evaluated 5.4 ± 0.4 years after irradiation to define the indications for GH treatment in these patients. Of
these, 63% had a low GH peak (<10 μg/l) after one (22 cases) or two (17 cases) stimulation tests. The plasma concentrations
of insulin-like growth factor I and its GH-dependent binding protein were normal for age in all but two cases. The height
changes between irradiation and evaluation were correlated with the GH peaks (P < 0.03) and were concordant, except in patients with early puberty. This occurred in 16 patients including all 12 girls irradiated
before 4 years of age. A significant (P < 0.03) reduction in height (SD) between irradiation and adult height occurred in untreated GH-deficient patients (−1 ± 0.3,
n = 6), but not in GH-deficient patients given GH (−0.6 ± 0.3, n = 8) or in those with normal GH peak (−0.4 ± 0.3, n = 7).
Conclusion In children irradiated for acute lymphoblastic leukaemia, GH deficiency is frequent after 18 Gy but its impact on adult height
is smaller than after higher doses. We suggest that the indications for gonadotropin releasing hormone analogue therapy should
be broad in patients with early or rapidly progressing puberty and those for GH therapy in those patients with a below average
constitutional height before irradiation.
Received: 17 November 1997 / Accepted: 9 February 1998 相似文献
11.
Genetic and long-term data on a patient with permanent isolated proximal renal tubular acidosis 总被引:1,自引:0,他引:1
A 12-year-old girl presented with permanent isolated proximal renal tubular acidosis (pRTA), glaucoma, band keratopathy,
mild cataract and short stature. Severe metabolic acidosis was caused by the impairment of bicarbonate reabsorption in the
proximal tubules and alkali therapy improved her acidaemia. A homozygous G to A transition at nucleotide 1,678 in the basolateral
kidney type Na+/HCO3
− (kNBC) co-transporter gene SLC4A4, which is critical in HCO3
− resorption in renal proximal tubules, was identified. Her height and height velocity (HV) were very low (−4.0 SD and −4.4 SD,
respectively) before alkali treatment, but both improved after initiating alkali therapy at the age of 2 years and 3 months.
The patient's body height and HV were 131.5 cm (−2.7 SD) and 4.0 cm (−2.0 SD), respectively at the age of 12 years.
Conclusion This case demonstrates that early administration of alkali therapy and sustained correction of acidosis, even if inadequate
to correct the metabolic acidosis, can markedly improves growth in permanent isolated proximal renal tubular acidosis.
Received: 3 April 2000 / Accepted: 5 July 2000 相似文献
12.
Pituitary dysfunction, morbidity and mortality with congenital midline malformation of the cerebrum 总被引:1,自引:0,他引:1
The purpose of this study was to review systematically a series of patients with congenital midline brain defects and pituitary
dysfunction in early childhood and to quantitate the degree of dysfunction and clinical outcome. This study was a retrospective
analysis of case notes of patients with pituitary dysfunction associated with either a midline cerebral anomaly and/or optic
nerve hypoplasia. Forty patients were studied: 2 with semilobar holoprosencephaly, 2 with lobar holoprosencephaly, 18 with
septo-optic dysplasia with an intact septum pellucidum, 7 with septo-optic dysplasia with an absent septum pellucidum, 7 with
agenesis of the corpus callosum and 4 patients with isolated pituitary hypoplasia. An early age of diagnosis, feeding difficulties,
neurodevelopmental disability, visual impairment and seizures were common occurrences. Despite disordered neuro-anatomy, most
seizure disorders were caused by hypoglycaemia or hypernatraemia. Hypotensive/hypoglycaemic crises accounted for two out of
three deaths within the study population. Most of patients had multiple pituitary hormone deficiency with growth hormone and
Adreo corticotrophic hormone deficiency occurring most commonly. Unequivocal isolated hypothalamic dysfunction was an uncommon
finding. In congenital midline brain malformation there is a spectrum of disordered neuro-anatomy associated with variable
pituitary dysfunction. Clinical manifestations such as convulsions and developmental delay may be due to disordered metabolism
and/or neuro-anatomy.
Conclusion Children with congenital midline brain defects frequently manifest convulsions, neurodevelopmental disability and poor growth
due to disordered metabolism and/or neuro-anatomy. Treating clinicians must be aware of the complex, dynamic neurological
and metabolic nature of these patients and their potential for early demise.
Received: 9 February 1998 / Accepted in revised form: 29 July 1998 相似文献
13.
R. W. Holl R. Pfäffle C. Kim W. Sorgo W. M. Teller G. Heimann 《European journal of pediatrics》1997,156(11):835-837
A child exhibited postnatal obstipation and icterus together with severe growth failure during the 1st year of life, a small
facial skull and a prominent forehead. Endocrine work-up established the diagnosis of combined pituitary deficiencies of growth
hormone, TSH and prolactin. Subsequently, the Pit-1 gene was analysed in the patient and both parents. A single point mutation
was detected in exon 6 of the child: a C to G transversion on one allele, causing arginine in position 271 to be substituted
by tryptophan (R271 W). This position is known as a “hot spot” for mutations. The inheritance is autosomal-dominant, as the
mutated gene product interferes with DNA-binding of the wild-type protein. In contrast, other mutations in the PIT-1 gene
are inherited in an autosomal-recessive mode.
Conclusion Diagnosing Pit-1 gene mutations as a rare cause of combined pituitary deficiency is important both for genetic counselling
as well as for predicting the future course in the patient (spontaneous puberty, no glucocorticoid substitution necessary
during stress periods).
Received: 13 January 1997 / Accepted: 10 May 1997 相似文献
14.
J. Dötsch T. Siebler W. F. Blum W. Rascher W. Kiess 《European journal of pediatrics》1998,157(9):712-714
A 12.5-year-old girl presented with short stature. Insulin-like growth factor 1(IGF-I) and insulin- like growth factor binding
protein (IGFBP-3) were below the 0.1 percentile. Growth hormone provocation tests disclosed normal responses to l-arginine and insulin-induced hypoglycaemia. A huge benign mesenteric cyst was discovered by abdominal ultrasound and completely
removed. Subsequently, the girl showed a marked catch-up growth; however, IGF-I and IGFBP-3 remained below the 0.1 percentile.
Conclusion These observations imply that growth may take place even with very low levels of insulin-like growth factors. The interpretation
of low IGF-I and IGFBP-3 levels in short children still requires good clinical judgement and basic knowledge of their biological
action.
Received: 24 September 1997 / Accepted in revised form: 16 March 1998 相似文献
15.
Mitochondrial DNA deletion with Kearns Sayre syndrome in a child with Addison disease 总被引:3,自引:0,他引:3
R. G. Boles T. Roe D. Senadheera V. Mahnovski L. J. C. Wong 《European journal of pediatrics》1998,157(8):643-647
Kearns Sayre syndrome (KSS) is a multisystem disorder with a confounding variety of clinical manifestations, including ocular
myopathy, pigmentary retinopathy, heart block and ataxia. Endocrinopathies are common in KSS, including growth hormone deficiency,
hypogonadism, diabetes mellitus and hypoparathyroidism. A variety of deletions of mitochondrial DNA (mtDNA) are found in
most cases. We report on a 5-year-old boy with Addison disease in whom further investigation revealed a 4.9 kilobase mtDNA
deletion and KSS. Later he developed severe lactic acidosis and expired.
Conclusion The degree of mutant mtDNA heteroplasmy in various tissues on autopsy did not correlate well with the clinical manifestations,
although this may be due at least in part to replacement with other tissue types. Our report is the first of non-autoimmune
Addison disease in KSS and patients with KSS should be evaluated for adrenal insufficiency. Early recognition of adrenal insufficiency
is crucial to prevent mortality from this cause.
Received: 1 October 1997 / Accepted: 11 March 1998 相似文献
16.
U. Eiholzer K. Stutz C. Weinmann T. Torresani L. Molinari A. Prader 《European journal of pediatrics》1998,157(11):890-893
It is well established that insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3)
and insulin are low in growth hormone deficiency, but due to their dependence on nutrition, they are elevated in healthy obese
children. As the presence of growth hormone deficiency in Prader-Labhart-Willi syndrome (PWS) is still controversial, we studied
insulin, IGF-I and IGFBP-3 levels in 19 children with PWS (age range 0.5–14.6 years). Serum concentrations of insulin (SDS:
−0.7±0.9, P=0.01) and IGF-I (SDS: −0.7±0.8,P=0.002) were low, but IGFBP-3 (SDS: −0.3±1.2, P=0.2) was normal compared to normal weight age-matched children. Since children with PWS are typically obese, insulin, IGF-I
and IGFBP-3 levels should be compared to normal obese children who present increased levels of these hormones. In comparison
to data of healthy obese children reported in the literature, not only IGF-I, but also IGFBP-3 levels are low and fasting
insulin levels even very low, suggesting a growth hormone deficiency.
Received: 19 November 1997 / Accepted in revised form: 2 March 1998 相似文献
17.
Adan L Bussières L Dinand V Zerah M Pierre-Kahn A Brauner R 《European journal of pediatrics》2000,159(5):348-355
A suprasellar arachnoid cyst may cause disorders of growth, puberty and hypothalamic-pituitary function, due to the proximity
of the cyst to the hypothalamic-pituitary area. A total of 30 patients (17 boys) with cyst diagnosed at 4.3 ± 1 years were
routinely evaluated at 5.4 ± 1 years; 24 of them had one or multiple cyst derivations. Some 23 cases had an abnormal height,
weight or puberty: short (<−2SD, 5 cases) or tall (>2SD, 10 cases) stature, overweight (body mass index, BMI, >2SD, 6 cases),
central precocious puberty (10 cases) and/or no progression of pubertal development (3 cases). The growth hormone (GH) peaks
after pharmacological stimulation test were low (<10 μg/l) in 16 patients, confirmed by a second evaluation in 8/11 of them.
The plasma free thyroxine was low in five patients, prolactin was high in two and the cortisol and concomitant plasma and
urinary osmolalities were normal. BMI was correlated negatively with the GH peaks (r=−0.37, P < 0.01) and positively with the plasma leptin concentrations (r=0.55, P < 0.01). The plasma fasting insulin concentrations were also correlated negatively with the GH peaks (r=−0.55, P < 0.02) and positively with the plasma insulin-like growth factor I concentrations (r=0.64, P < 0.002). The adult height (12 cases) was at 4SD in 1 and <−2SD in 4 patients, two of whom had precocious puberty untreated
with gonadotropin releasing hormone (GnRH) analogue, and two had untreated GH deficiency. The adult height of those treated
was normal. One girl had primary amenorrhoea and two boys had low plasma testosterone, despite a normal gonadotropin response
to a GnRH test.
Conclusion Suprasellar arachnoid cysts may cause deficiencies of growth hormone and thyrotropin, stimulation of the hypothalamic-pituitary-gonadal
axis, tall stature and/or overweight. These last two disorders may be due to hyperinsulinism, itself due to suprasellar arachnoid
cyst.
Received: 5 May 1999 / Accepted: 28 October 1999 相似文献
18.
J. Hendrickx N. U. Bosshard P. Willems R. Gitzelmann 《European journal of pediatrics》1998,157(11):919-923
Phosphorylase kinase (PHK) is a regulatory enzyme in glycogen metabolism. Mutations in the gene encoding the α subunit of
PHK (PHKA2) have been shown to be responsible for X-linked liver glycogenosis (XLG). XLG, a frequent type of glycogen storage
disease, is characterised by hepatomegaly and growth retardation. Two subtypes of XLG have been described: XLG type I patients
have a clear-cut PHK deficiency in liver and blood cells, whereas XLG type II patients have a normal or residual activity.
Here, we present clinical, biochemical and molecular findings on a liver glycogenosis patient in whom the diagnosis XLG II
only became clear after enzyme assays in the liver and identification of the disease-causing mutation. A missense mutation
replacing arginine at amino acid position 186 by histidine (R186H) was identified in the PHKA2 gene. Mutations of the same
arginine residue have been previously found in at least four other unrelated XLG II patients.
Conclusion Arginine at position 186 of the α subunit seems to play an important role in the structure or the regulation of PHK. In patients
with XLG having normal or residual PHK activity where XLG II is suspected, the identification of mutations in PHKA2 leads
to the final classification.
Received: 19 December 1997 / Accepted in revised form: 30 March 1998 相似文献
19.
Cerebral palsy and pyruvate dehydrogenase deficiency: identification of two new mutations in the E1α gene 总被引:2,自引:0,他引:2
W. Lissens P. Vreken P. G. Barth F. A. Wijburg W. Ruitenbeek R. J. A. Wanders S. Seneca I. Liebaers L. De Meirleir 《European journal of pediatrics》1999,158(10):853-857
Pyruvate dehydrogenase (PDH) complex deficiency, a common cause of congenital lactic acidosis, is mostly due to mutations
in the X-linked gene coding for the E1α subunit of the complex. We have studied two unrelated girls presenting a static encephalopathy
with spastic quadriplegia, microcephaly and seizures and in one girl, hypocalcaemia, a new finding in PDH complex deficiency.
PDH deficiency was diagnosed in adolescence and both girls had low PDH complex activity in muscle but normal amounts of all
subunits on Western blotting, and a normal lactate/pyruvate ratio in blood and CSF. Mutation analysis of the E1α gene at the
cDNA or DNA level revealed an arginine to histidine substitution at amino acid position 288 (R288H) in the girl with hypocalcaemia
and a 12 bp insertion, predicting a four amino acid duplication at the c-terminal end of the protein in the second girl. They
both carried a normal and a mutated E1α gene and X-inactivation studies showed skewed patterns.
Conclusion Mutation identification in pyruvate dehydrogenase complex deficiency remains important especially for the determination of
the recurrence risk and for reliable genetic counselling in couples with an affected child.
Received: 24 November 1998 / Accepted: 20 March 1999 相似文献
20.
C. Steen E. R. Baumgartner M. Duran W. Lehnert T. Suormala R. Fingerhut M. Stehn A. Kohlschütter 《European journal of pediatrics》1999,158(9):730-733
A mildly retarded infant with failure to thrive developed hypoglycaemia, focal seizures, respiratory failure and hemiparesis
during a febrile episode at the age of 16 months. A brain scan was initially normal and showed hemilateral focal edema and
gliosis at later stages. 3-Methylcrotonyl-CoA carboxylase deficiency was suggested by elevated urinary excretion of 3-hydroxyisovaleric
acid and 3-methylcrotonylglycine, and confirmed by enzyme assays. The patient was treated with protein restriction and carnitine
and remained stable during the following 5 years. Hemiparesis and some developmental delay persisted.
Conclusion In acute focal brain disease, metabolic disorders must be considered. 3-Methylcrotonyl-CoA carboxylase deficiency adds to
the list of possible causes of “metabolic stroke”.
Received: 24 March 1998 / Accepted in revised form: 29 December 1998 相似文献